The Anx7 gene codes for a Ca(2+)/GTPase with calcium channel and membrane fusion properties that has been proposed to regulate exocytotic secretion in chromaffin and other cell types. We have previously reported that the homozygous Anx7 (+/-) knockout mouse has an embryonically lethal phenotype. However, the viable heterozygous Anx7 (+/-) mouse displays a complex phenotype that includes adrenal gland hypertrophy, chromaffin cell hyperplasia, and defective IP(3) receptor (IP(3)R) expression. To search for a molecular basis for this phenotype, we have used cDNA microarray technology and have challenged control and mutant mice with fed or fasting conditions. We report that in the absence of the Anx7/IP(3)R signaling system, the cells in the adrenal gland are unable to discriminate between the fed and fasted states, in vivo. In control chromaffin cells, fasting is accompanied by an increased expression of structural genes for chromaffin cell contents, including chromogranin A and B, and DbetaH. There are also genes whose expression is specifically reduced. However, the Anx7 (+/-) mutation results in sustained expression of these nutritionally sensitive genes. We hypothesize that the calcium signaling defect due to the missing IP(3)R may be responsible for the global effects of the mutation on nutritionally sensitive genes. We further hypothesize that the tonically elevated expression of chromogranin A, a reportedly master control "switch" for dense core granule formation, may contribute to the process driving glandular hypertrophy and chromaffin cell hyperplasia in the Anx7 (+/-) mutant mouse.